The objective of the proposed research program is to further our understanding of the cellular and molecular mechanisms underlying the formation of specific retinogeniculate projections in the primate visual system. We will focus on the development of the two major functional streams, magnocellular (M) and parvocellular (P), which at maturity are a hallmark of the primate visual system. In Specific Aim 1, we will utilize modern neuroanatomical tracing methods in combination with pre- and postsynaptic molecular markers to learn how the formation of M and P pathways relates to synapse formation in the dLGN. Our working hypotheses are: (i) that eye-specific inputs form in the P pathway earlier than in the M pathway, and (ii) that selective ingrowth of retinal fibers into the P and/or M subdivisions of the dLGN occurs prior to synaptogenesis. In Specific Aim 2 we will define the spatiotemporal properties of retinal activity during the time that retinal axons selectively innervate the M and P segments of the dLGN. If correlated retinal activity is observed at this early stage of development, we will assess the effects of perturbing and also blocking such activity on the formation of M and P retinogeniculate projections using a novel immunotoxin developed in our laboratory. The foregoing experiments will tell us whether or not neuronal activity plays a role in the development of these two functionally distinct pathways. In Specific Aim 3 we will utilize DNA microarrays and in situ hybridization methods to find molecular cues expressed in the developing dLGN during the period when M and P pathways are being formed. The proposed research program will break new ground by increasing our understanding of the mechanisms underlying the formation of M and P pathways which are a distinguishing feature of the primate visual system.